| 1. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 2. |
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| 3. |
- Bartelt, Alexander, et al.
(författare)
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Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in response to pharmacological stimulation of thermogenesis linked to increased HDL levels in APOE(star)3-Leiden. CETP mice. Both cold-induced and pharmacological thermogenic activation enhances HDL remodelling, which is associated with specific lipidomic changes in mouse and human HDL. Furthermore, thermogenic stimulation promotes HDL-cholesterol clearance and increases macrophage-to-faeces reverse cholesterol transport in mice. Mechanistically, we show that intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL by scavenger receptor B-I are the driving forces of HDL-cholesterol disposal in liver. Our findings corroborate the notion that high metabolic activity of thermogenic adipocytes confers atheroprotective properties via increased systemic cholesterol flux through the HDL compartment.
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| 4. |
- Burström, Lage, 1954-, et al.
(författare)
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Acute effects of vibration on thermal perception thresholds
- 2006
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Ingår i: Diagnosis of injuries caused by hand-transmitted vibration - 2nd International workshop, Göteborg, 2006. - : Springer Science and Business Media LLC.
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Konferensbidrag (refereegranskat)abstract
- Objective This study focuses on the acute effects of vibration and how vibrations influence the measures of the thermal perception thresholds during different vibration magnitudes, frequencies, and durations.Methods The fingers of ten healthy subjects, five males and five females, were exposed to vibration under 16 conditions with a combination of different frequency, intensity and exposure time. The vibration frequency was 31.5 and 125 Hz and exposure lasted between 2 and 16 min. The energy-equivalent frequency weighted acceleration, according to ISO 5349-1, for the experimental time of 16 min was 2.5 or 5.0 m/s(2) (r.m.s.), corresponding to a 8-h equivalent acceleration, A(8) of 0.46 and 0.92 m/s(2), respectively. A measure of the thermal perception of cold and warmth was conducted before the different exposures to vibration. Immediately after the vibration exposure the acute effect was measured continuously on the exposed index finger for the first 75 s, followed by 30 s of measures at every minute for a maximum of 10 min. If the subject's thermal thresholds had not recovered, the measures continued for a maximum of 30 min with measurements taken every 5 min.Results For all experimental conditions and 30 s after exposure, the mean changes of the thresholds compared with the pre-test were found to be 0.05 and -0.67C for the warmth and cold thresholds, respectively. The effect of the vibration exposure was only significant on the cold threshold and only for the first minute after exposure when the threshold was decreased. The warmth threshold was not significantly affected at all. The frequency and the exposure time of the vibration stimuli had no significant influence on the perception thresholds for the sensation of cold or warmth. Increased equivalent frequency weighted acceleration resulted in a significant decrease of the subjects' cold threshold, not the warmth. The thresholds were unaffected when changes in the vibration magnitude were expressed as the frequency weighted acceleration or the unweighted acceleration.Conclusion When testing for the thermotactile thresholds, exposure to vibration on the day of a test might influence the results. Until further knowledge is obtained the previous praxis of 2 h avoidance of vibration exposure before assessment is recommended.
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| 5. |
- André, Domenique, et al.
(författare)
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FLOWERING LOCUS T paralogs control the annual growth cycle in Populus trees
- 2022
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Ingår i: Current Biology. - : Cell Press. - 0960-9822 .- 1879-0445. ; 32:13, s. 2988-2996.e4
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Tidskriftsartikel (refereegranskat)abstract
- In temperate and boreal regions, perennials adapt their annual growth cycle to the change of seasons. These adaptations ensure survival in harsh environmental conditions, allowing growth at different latitudes and altitudes, and are therefore tightly regulated. Populus tree species cease growth and form terminal buds in autumn when photoperiod falls below a certain threshold.1 This is followed by establishment of dormancy and cold hardiness over the winter. At the center of the photoperiodic pathway in Populus is the gene FLOWERING LOCUS T2 (FT2), which is expressed during summer and harbors significant SNPs in its locus associated with timing of bud set.1–4 The paralogous gene FT1, on the other hand, is hyper-induced in chilling buds during winter.3,5 Even though its function is so far unknown, it has been suggested to be involved in the regulation of flowering and the release of winter dormancy.3,5 In this study, we employ CRISPR-Cas9-mediated gene editing to individually study the function of the FT-like genes in Populus trees. We show that while FT2 is required for vegetative growth during spring and summer and regulates the entry into dormancy, expression of FT1 is absolutely required for bud flush in spring. Gene expression profiling suggests that this function of FT1 is linked to the release of winter dormancy rather than to the regulation of bud flush per se. These data show how FT duplication and sub-functionalization have allowed Populus trees to regulate two completely different and major developmental control points during the yearly growth cycle.
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| 6. |
- Aspholm-Hurtig, Marina, et al.
(författare)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 7. |
- Birve, Anna, et al.
(författare)
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A novel SOD1 splice site mutation associated with familial ALS revealed by SOD activity analysis
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:21, s. 4201-4206
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Tidskriftsartikel (refereegranskat)abstract
- More than 145 mutations have been found in the gene CuZn-Superoxide dismutase (SOD1) in patients with amyotrophic lateral sclerosis (ALS). The vast majority are easily detected nucleotide mutations in the coding region. In a patient from a Swiss ALS family with half-normal erythrocyte SOD1 activity, exon flanking sequence analysis revealed a novel thymine to guanine mutation 7 bp upstream of exon 4 (c.240-7T>G). The results of splicing algorithm analyses were ambiguous, but five out of seven analysis tools suggested a potential novel splice site that would add six new base pairs to the mRNA. If translated, this mRNA would insert Ser and Ile between Glu78 and Arg79 in the SOD1 protein. In fibroblasts from the patient, the predicted mutant transcript and the mutant protein were both highly expressed, and despite the location of the insertion into the metal ion-binding loop IV, the SOD1 activity appeared high. In erythrocytes, which lack protein synthesis and are old compared with cultured fibroblasts, both SOD1 protein and enzymic activity was 50% of controls. Thus, the usage of the novel splice site is near 100%, and the mutant SOD1 shows the reduced stability typical of ALS-associated mutant SOD1s. The findings suggests that this novel intronic mutation is causing the disease and highlights the importance of wide exon-flanking sequencing and transcript analysis combined with erythrocyte SOD1 activity analysis in comprehensive search for SOD1 mutations in ALS. We find that there are potentially more SOD1 mutations than previously reported.
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| 8. |
- Blomquist, Tomas, et al.
(författare)
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Development of virtual teams and learning communities
- 2006
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Ingår i: Collaborating virtually. - Punjagutta, India : Icfai University Press. - 8131403084 ; , s. 121-131
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Bokkapitel (refereegranskat)abstract
- Students of an Internet based course in project management worked during a 20 week period worked in teams of 4-6 persons. The course consisted of Swedish students living in Sweden or abroad, which made it impossible for many of the teams to have any face-to-face interaction. During the course, the teams were assigned a series of discussion questions and cases. The study, based on a survey of 287 students who participated in the course, examined their experience of teamwork and showed that many of the classical team development issues also evolve in a virtual team. Furthermore, the study showed that students considered their teamwork was efficient and that being able to communicate, discuss and share experiences was essential for developing a positive learning community.
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| 9. |
- Blomquist, Tomas, et al.
(författare)
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Project as practice : making project research matter
- 2006
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Ingår i: Proceedings of IRNOP VII project research conference. - Beijing : China Publishing House of Electronics Industry. - 712103252X ; , s. 540-549
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Konferensbidrag (refereegranskat)abstract
- Project theory is not only an immature field of research, it is insubstantial when it comes to understanding what is really going on in projects. This paper contributes to making project research matter to the academic as well as the practitioner through the theoretical development of a project-as-practice approach, aligned with an ongoing debate in social science research. We outline the framework of project-as-practice and argue that there are two major challenges to the researcher: the relevance challenge and the pattern challenge. We suggest how these challenges can be met and give some examples of earlier studies that have done so. The practice approach is not a substitute to present theorizing but rather a complement that brings substance. Finally, underlying notions of the practice approach are outlined in order to have a fruitful future development of a project-as-practice approach that makes project theory matter!
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| 10. |
- Blomquist, Tomas, 1963-, et al.
(författare)
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Project-as-practice : in search of project management research that matters
- 2010
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Ingår i: Project Management Journal. - : SAGE Publications. - 8756-9728 .- 1938-9507. ; 41:1, s. 5-16
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Tidskriftsartikel (refereegranskat)abstract
- Research on projects is not only an immaturefield of research, but it is also insubstantial whenit comes to understanding what occurs in projects.This article contributes to making projectmanagement research matter to the academic aswell as to the practitioner by developing a projectas-practice approach, in alignment with theongoing debate in social science research.The article outlines a framework and argues thatthere are two major challenges to the researcherand also suggests how these challenges can bemet. Underlying notions of the practice approachare outlined to ensure a development of theproject-as-practice approach that makes projectmanagement research matter!
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